Base de dados : MEDLINE
Pesquisa : D08.811.277.352.650.775.400.400 [Categoria DeCS]
Referências encontradas : 259 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 26 ir para página                         

  1 / 259 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28257417
[Au] Autor:Chicote JU; DeSalle R; García-España A
[Ad] Endereço:Hospital Universitari de Tarragona Joan XXIII, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain.
[Ti] Título:Phosphotyrosine phosphatase R3 receptors: Origin, evolution and structural diversification.
[So] Source:PLoS One;12(3):e0172887, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Subtype R3 phosphotyrosine phosphatase receptors (R3 RPTPs) are single-spanning membrane proteins characterized by a unique modular composition of extracellular fibronectin repeats and a single cytoplasmatic protein tyrosine phosphatase (PTP) domain. Vertebrate R3 RPTPs consist of five members: PTPRB, PTPRJ, PTPRH and PTPRO, which dephosphorylate tyrosine residues, and PTPRQ, which dephosphorylates phophoinositides. R3 RPTPs are considered novel therapeutic targets in several pathologies such as ear diseases, nephrotic syndromes and cancer. R3 RPTP vertebrate receptors, as well as their known invertebrate counterparts from animal models: PTP52F, PTP10D and PTP4e from the fruitfly Drosophila melanogaster and F44G4.8/DEP-1 from the nematode Caenorhabditis elegans, participate in the regulation of cellular activities including cell growth and differentiation. Despite sharing structural and functional properties, the evolutionary relationships between vertebrate and invertebrate R3 RPTPs are not fully understood. Here we gathered R3 RPTPs from organisms covering a broad evolutionary distance, annotated their structure and analyzed their phylogenetic relationships. We show that R3 RPTPs (i) have probably originated in the common ancestor of animals (metazoans), (ii) are variants of a single ancestral gene in protostomes (arthropods, annelids and nematodes); (iii) a likely duplication of this ancestral gene in invertebrate deuterostomes (echinodermes, hemichordates and tunicates) generated the precursors of PTPRQ and PTPRB genes, and (iv) R3 RPTP groups are monophyletic in vertebrates and have specific conserved structural characteristics. These findings could have implications for the interpretation of past studies and provide a framework for future studies and functional analysis of this important family of proteins.
[Mh] Termos MeSH primário: Evolução Molecular
Filogenia
Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/genética
[Mh] Termos MeSH secundário: Animais
Caenorhabditis elegans/genética
Diferenciação Celular/genética
Sequência Conservada/genética
Proteínas de Drosophila/genética
Drosophila melanogaster/genética
Seres Humanos
Proteínas Tirosina Fosfatases/genética
Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/genética
Transdução de Sinais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drosophila Proteins); EC 3.1.3.48 (Protein Tyrosine Phosphatases); EC 3.1.3.48 (Ptp10D protein, Drosophila); EC 3.1.3.48 (Ptp4E protein, Drosophila); EC 3.1.3.48 (Ptp52F protein, Drosophila); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 3); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 4)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170304
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0172887


  2 / 259 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28235043
[Au] Autor:Bhattarai N; McLinden JH; Xiang J; Mathahs MM; Schmidt WN; Kaufman TM; Stapleton JT
[Ad] Endereço:Research and Medical Services, Iowa City Veterans Affairs Medical Center, Iowa City, Iowa, United States of America.
[Ti] Título:Hepatitis C virus infection inhibits a Src-kinase regulatory phosphatase and reduces T cell activation in vivo.
[So] Source:PLoS Pathog;13(2):e1006232, 2017 Feb.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Among human RNA viruses, hepatitis C virus (HCV) is unusual in that it causes persistent infection in the majority of infected people. To establish persistence, HCV evades host innate and adaptive immune responses by multiple mechanisms. Recent studies identified virus genome-derived small RNAs (vsRNAs) in HCV-infected cells; however, their biological significance during human HCV infection is unknown. One such vsRNA arising from the hepatitis C virus (HCV) E2 coding region impairs T cell receptor (TCR) signaling by reducing expression of a Src-kinase regulatory phosphatase (PTPRE) in vitro. Since TCR signaling is a critical first step in T cell activation, differentiation, and effector function, its inhibition may contribute towards HCV persistence in vivo. The effect of HCV infection on PTPRE expression in vivo has not been examined. Here, we found that PTPRE levels were significantly reduced in liver tissue and peripheral blood mononuclear cells (PBMCs) obtained from HCV-infected humans compared to uninfected controls. Loss of PTPRE expression impaired antigen-specific TCR signaling, and curative HCV therapy restored PTPRE expression in PBMCs; restoring antigen-specific TCR signaling defects. The extent of PTPRE expression correlated with the amount of sequence complementarity between the HCV E2 vsRNA and the PTPRE 3' UTR target sites. Transfection of a hepatocyte cell line with full-length HCV RNA or with synthetic HCV vsRNA duplexes inhibited PTPRE expression, recapitulating the in vivo observation. Together, these data demonstrate that HCV infection reduces PTPRE expression in the liver and PBMCs of infected humans, and suggest that the HCV E2 vsRNA is a novel viral factor that may contribute towards viral persistence.
[Mh] Termos MeSH primário: Hepatite C/imunologia
Evasão da Resposta Imune/imunologia
Ativação Linfocitária/imunologia
Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/imunologia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Ensaio de Imunoadsorção Enzimática
Hepacivirus/imunologia
Seres Humanos
Immunoblotting
RNA Viral/imunologia
Receptores de Antígenos de Linfócitos T/imunologia
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Viral); 0 (Receptors, Antigen, T-Cell); EC 3.1.3.48 (PTPRE protein, human); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 4)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170803
[Lr] Data última revisão:
170803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170225
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006232


  3 / 259 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28065597
[Au] Autor:Yao Z; Darowski K; St-Denis N; Wong V; Offensperger F; Villedieu A; Amin S; Malty R; Aoki H; Guo H; Xu Y; Iorio C; Kotlyar M; Emili A; Jurisica I; Neel BG; Babu M; Gingras AC; Stagljar I
[Ad] Endereço:Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
[Ti] Título:A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome.
[So] Source:Mol Cell;65(2):347-360, 2017 Jan 19.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Receptor tyrosine kinases (RTKs) and protein phosphatases comprise protein families that play crucial roles in cell signaling. We used two protein-protein interaction (PPI) approaches, the membrane yeast two-hybrid (MYTH) and the mammalian membrane two-hybrid (MaMTH), to map the PPIs between human RTKs and phosphatases. The resulting RTK-phosphatase interactome reveals a considerable number of previously unidentified interactions and suggests specific roles for different phosphatase families. Additionally, the differential PPIs of some protein tyrosine phosphatases (PTPs) and their mutants suggest diverse mechanisms of these PTPs in the regulation of RTK signaling. We further found that PTPRH and PTPRB directly dephosphorylate EGFR and repress its downstream signaling. By contrast, PTPRA plays a dual role in EGFR signaling: besides facilitating EGFR dephosphorylation, it enhances downstream ERK signaling by activating SRC. This comprehensive RTK-phosphatase interactome study provides a broad and deep view of RTK signaling.
[Mh] Termos MeSH primário: Mapas de Interação de Proteínas
Receptor do Fator de Crescimento Epidérmico/metabolismo
Transdução de Sinais
Quinases da Família src/metabolismo
[Mh] Termos MeSH secundário: Animais
Ativação Enzimática
Fator de Crescimento Epidérmico/farmacologia
Células HEK293
Seres Humanos
Camundongos
Mutação
Fosforilação
Mapeamento de Interação de Proteínas
Receptor do Fator de Crescimento Epidérmico/agonistas
Receptor do Fator de Crescimento Epidérmico/genética
Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/genética
Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/metabolismo
Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/genética
Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/metabolismo
Reprodutibilidade dos Testes
Transdução de Sinais/efeitos dos fármacos
Transfecção
Técnicas do Sistema de Duplo-Híbrido
Quinases da Família src/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
62229-50-9 (Epidermal Growth Factor); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 2.7.10.2 (src-Family Kinases); EC 3.1.3.48 (PTPRA protein, human); EC 3.1.3.48 (PTPRB protein, human); EC 3.1.3.48 (PTPRH protein, human); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 3); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 4)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170110
[St] Status:MEDLINE


  4 / 259 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27965091
[Au] Autor:Xiao J; Gao Y; Yang F; Wang C; Xu Y; Chang R; Zha X; Wang L
[Ad] Endereço:Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China; Key Laboratory of Glycoconjugate Research, Ministry of Health, Shanghai, China.
[Ti] Título:ß1,6 GlcNAc branches-modified protein tyrosine phosphatase alpha enhances its stability and promotes focal adhesion formation in MCF-7 cells.
[So] Source:Biochem Biophys Res Commun;482(4):1455-1461, 2017 Jan 22.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Receptor-like protein tyrosine phosphatase alpha (RPTPα or PTPα), a type I transmembrane glycoprotein with complex N-glycans, executes multifunction roles on cell behaviors. However, its effect on tumorigenesis and metastasis remains controversial. In this study, PTPα is identified as a novel substrate of N-Acetylglucosaminyltransferase V (GnT-V). Immunofluorescence results showed that addition of ß1,6 GlcNAc branches on PTPα enhanced PTPα's cytomembrane assemble in GnT-V-MCF-7 compared with Mock-MCF-7 (MCF7 cells transfected with the vector pcDNA3). Then we found the alleviating degradation of PTPα was observed in GnT-V-MCF-7 while PTPα in Mock-MCF-7 was prone to quick degradation. Increased cell-surface retention subsequently enhanced PTPα's catalytic activity on the dephosphorylation of Src kinase at Tyr529 and promoted focal adhesion formation and mature. Therefore, our findings could provide an insight into the molecular mechanism of how GnT-V promoted cell migration, suggesting that PTPα could be one of factors regulating promote migration of breast cancer cell.
[Mh] Termos MeSH primário: Adesões Focais/metabolismo
N-Acetilglucosaminiltransferases/metabolismo
Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/metabolismo
[Mh] Termos MeSH secundário: Neoplasias da Mama/metabolismo
Carcinogênese
Catálise
Linhagem Celular Tumoral
Movimento Celular
Feminino
Glicosilação
Seres Humanos
Integrina beta1/metabolismo
Lectinas/química
Células MCF-7
Metástase Neoplásica
Fosforilação
Plasmídeos/metabolismo
Polissacarídeos/química
Interferência de RNA
RNA Interferente Pequeno/metabolismo
Quinases da Família src/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Integrin beta1); 0 (Lectins); 0 (Polysaccharides); 0 (RNA, Small Interfering); EC 2.4.1.- (N-Acetylglucosaminyltransferases); EC 2.4.1.150 (N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase); EC 2.7.10.2 (src-Family Kinases); EC 3.1.3.48 (PTPRA protein, human); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 4)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161215
[St] Status:MEDLINE


  5 / 259 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27458171
[Au] Autor:Lee JH; Kim C; Baek SH; Ko JH; Lee SG; Yang WM; Um JY; Sethi G; Ahn KS
[Ad] Endereço:College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
[Ti] Título:Capsazepine inhibits JAK/STAT3 signaling, tumor growth, and cell survival in prostate cancer.
[So] Source:Oncotarget;8(11):17700-17711, 2017 Mar 14.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Persistent STAT3 activation is seen in many tumor cells and promotes malignant transformation. Here, we investigated whether capsazepine (Capz), a synthetic analogue of capsaicin, exerts anticancer effects by inhibiting STAT3 activation in prostate cancer cells. Capz inhibited both constitutive and induced STAT3 activation in human prostate carcinoma cells. Capz also inhibited activation of the upstream kinases JAK1/2 and c-Src. The phosphatase inhibitor pervanadate reversed Capz-induced STAT3 inhibition, indicating that the effect of Capz depends on a protein tyrosine phosphatase. Capz treatment increased PTPε protein and mRNA levels. Moreover, siRNA-mediated knockdown of PTPε reversed the Capz-induced induction of PTPε and inhibition of STAT3 activation, indicating that PTPε is crucial for Capz-dependent STAT3 dephosphorylation. Capz also decreased levels of the protein products of various oncogenes, which in turn inhibited proliferation and invasion and induced apoptosis. Finally, intraperitoneal Capz administration decreased tumor growth in a xenograft mouse prostate cancer model and reduced p-STAT3 and Ki-67 expression. These data suggest that Capz is a novel pharmacological inhibitor of STAT3 activation with several anticancer effects in prostate cancer cells.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Capsaicina/análogos & derivados
Janus Quinase 1/antagonistas & inibidores
Neoplasias da Próstata/tratamento farmacológico
Fator de Transcrição STAT3/antagonistas & inibidores
[Mh] Termos MeSH secundário: Células A549
Animais
Apoptose/efeitos dos fármacos
Capsaicina/farmacologia
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Ativação Enzimática/efeitos dos fármacos
Seres Humanos
Janus Quinase 1/metabolismo
Antígeno Ki-67/biossíntese
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Invasividade Neoplásica/patologia
Fosforilação
Neoplasias da Próstata/patologia
Proteínas Tirosina Fosfatases/antagonistas & inibidores
Interferência de RNA
RNA Interferente Pequeno/genética
Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/genética
Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/metabolismo
Fator de Transcrição STAT3/metabolismo
Vanadatos/farmacologia
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Ki-67 Antigen); 0 (RNA, Small Interfering); 0 (STAT3 Transcription Factor); 0 (STAT3 protein, human); 0 (pervanadate); 3WHH0066W5 (Vanadates); EC 2.7.10.2 (JAK1 protein, human); EC 2.7.10.2 (Janus Kinase 1); EC 3.1.3.48 (PTPRE protein, human); EC 3.1.3.48 (Protein Tyrosine Phosphatases); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 4); LFW48MY844 (capsazepine); S07O44R1ZM (Capsaicin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160727
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.10775


  6 / 259 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26911335
[Au] Autor:Kim C; Baek SH; Um JY; Shim BS; Ahn KS
[Ad] Endereço:Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemungu, Seoul, 130-701, Republic of Korea. sunny10526@nate.com.
[Ti] Título:Resveratrol attenuates constitutive STAT3 and STAT5 activation through induction of PTPε and SHP-2 tyrosine phosphatases and potentiates sorafenib-induced apoptosis in renal cell carcinoma.
[So] Source:BMC Nephrol;17:19, 2016 Feb 25.
[Is] ISSN:1471-2369
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Signal transducers and activators of transcription (STAT) proteins are critical transcription factor that are aberrantly activated in various types of malignancies, including renal cell carcinoma (RCC). METHODS: We investigated the effect of resveratrol (RES), an edible polyphenol phytoalexin on STAT3 and STAT5 activation cascade in both Caki-1 and 786-O RCC cell lines. RESULTS: We found that RES suppressed both constitutive STAT3 (tyrosine residue 705 and serine residue 727) and STAT5 (tyrosine residue 694 and 699) activation, which correlated with the suppression of the upstream kinases (JAK1, JAK2, and c-Src) in RCC. Also, RES abrogated DNA binding capacity and nuclear translocation of these two transcription factors. RES-induced an increased expression of PTPε and SHP-2 and the deletion of these two genes by small interfering RNA abolished the ability of RES to inhibit STAT3 activation, suggesting the critical role of both PTPε and SHP-2 in its possible mechanism of action. Moreover, RES induced S phase cell cycle arrest, caused induction of apoptosis, loss of mitochondrial membrane potential, and suppressed colony formation in RCC. We also found that RES downregulated the expression of STAT3/5-regulated antiapoptotic, proliferative, and metastatic gene products; and this correlated with induction of caspase-3 activation and anti-invasive activity. Beside, RES potentiated sorafenib induced inhibitory effect on constitutive STAT3 and STAT5 phosphorylation, apoptotic effects in 786-O cells, and this correlated with down-regulation of various oncogenic gene products. CONCLUSION: Overall, our results suggest that RES is a blocker of both STAT3 and STAT5 activation and thus may exert potential growth inhibitory effects against RCC cells.
[Mh] Termos MeSH primário: Antineoplásicos Fitogênicos/farmacologia
Apoptose/efeitos dos fármacos
Carcinoma de Células Renais/tratamento farmacológico
Neoplasias Renais/tratamento farmacológico
Fator de Transcrição STAT3/efeitos dos fármacos
Fator de Transcrição STAT5/efeitos dos fármacos
Estilbenos/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/farmacologia
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Seres Humanos
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Niacinamida/análogos & derivados
Niacinamida/farmacologia
Compostos de Fenilureia/farmacologia
Proteína Tirosina Fosfatase não Receptora Tipo 11/efeitos dos fármacos
Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo
Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/efeitos dos fármacos
Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/metabolismo
Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos
Fator de Transcrição STAT3/metabolismo
Fator de Transcrição STAT5/metabolismo
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Antineoplastic Agents, Phytogenic); 0 (Phenylurea Compounds); 0 (STAT3 Transcription Factor); 0 (STAT3 protein, human); 0 (STAT5 Transcription Factor); 0 (Stilbenes); 25X51I8RD4 (Niacinamide); 9ZOQ3TZI87 (sorafenib); EC 3.1.3.48 (PTPN11 protein, human); EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 4); Q369O8926L (resveratrol)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160226
[St] Status:MEDLINE
[do] DOI:10.1186/s12882-016-0233-7


  7 / 259 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26611753
[Au] Autor:Wang Q; Wang Y; Downey GP; Plotnikov S; McCulloch CA
[Ad] Endereço:Matrix Dynamics Group, University of Toronto, Ontario, Canada, M5S 3E2.
[Ti] Título:A ternary complex comprising FAK, PTPα and IP3 receptor 1 functionally engages focal adhesions and the endoplasmic reticulum to mediate IL-1-induced Ca2+ signalling in fibroblasts.
[So] Source:Biochem J;473(4):397-410, 2016 Feb 15.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ca(2+) release is tightly sequestered in eukaryotic cells to enable fine spatio-temporal control of signalling but how Ca(2+) release from the endoplasmic reticulum (ER) is linked to cell adhesions is not defined. We examined the spatial restriction of Ca(2+) release through the inositol 1,4,5-triphosphate receptor 1 (IP3R1) in response to interleukin-1 (IL-1) and the functions of the adhesion-associated proteins, focal adhesion kinase (FAK) and protein tyrosine phosphatase-α (PTPα). In cultured fibroblasts IL-1 treatment promoted co-localization of PTPα and FAK with the ER and increased association of IP3R1 with PTPα and FAK at focal adhesions (FAs). GST pull-down assays of purified proteins demonstrated that PTPα and FAK directly interacted with IP3R1. These interactions depended on the focal adhesion-targeting (FAT) and band4.1-ezrin-radixin-moesin (FERM) domains of FAK. PTPα was required for the association of IP3R1 with Src, which mediated IP3R1 phosphorylation and consequently ER Ca(2+) release. Collectively, these data indicate that PTPα and FAK, which are enriched in FAs, interact with IP3R1 at adjacent ER sites to spatially sequester IL-1-induced Ca(2+) signalling.
[Mh] Termos MeSH primário: Sinalização do Cálcio/efeitos dos fármacos
Retículo Endoplasmático/metabolismo
Proteína-Tirosina Quinases de Adesão Focal/metabolismo
Adesões Focais
Receptores de Inositol 1,4,5-Trifosfato/metabolismo
Interleucina-1/farmacologia
Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Fibroblastos/efeitos dos fármacos
Fibroblastos/metabolismo
Proteína-Tirosina Quinases de Adesão Focal/genética
Camundongos
Camundongos Knockout
Ligação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Inositol 1,4,5-Trisphosphate Receptors); 0 (Interleukin-1); 0 (Itpr1 protein, mouse); EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 4)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151128
[St] Status:MEDLINE
[do] DOI:10.1042/BJ20150907


  8 / 259 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26414708
[Au] Autor:Stanford SM; Svensson MN; Sacchetti C; Pilo CA; Wu DJ; Kiosses WB; Hellvard A; Bergum B; Muench GR; Elly C; Liu YC; den Hertog J; Elson A; Sap J; Mydel P; Boyle DL; Corr M; Firestein GS; Bottini N
[Ad] Endereço:La Jolla Institute for Allergy and Immunology, La Jolla, California.
[Ti] Título:Receptor Protein Tyrosine Phosphatase α-Mediated Enhancement of Rheumatoid Synovial Fibroblast Signaling and Promotion of Arthritis in Mice.
[So] Source:Arthritis Rheumatol;68(2):359-69, 2016 Feb.
[Is] ISSN:2326-5205
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: During rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) critically promote disease pathogenesis by aggressively invading the extracellular matrix of the joint. The focal adhesion kinase (FAK) signaling pathway is emerging as a contributor to the anomalous behavior of RA FLS. The receptor protein tyrosine phosphatase α (RPTPα), which is encoded by the PTPRA gene, is a key promoter of FAK signaling. The aim of this study was to investigate whether RPTPα mediates FLS aggressiveness and RA pathogenesis. METHODS: Through RPTPα knockdown, we assessed FLS gene expression by quantitative polymerase chain reaction analysis and enzyme-linked immunosorbent assay, invasion and migration by Transwell assays, survival by annexin V and propidium iodide staining, adhesion and spreading by immunofluorescence microscopy, and activation of signaling pathways by Western blotting of FLS lysates. Arthritis development was examined in RPTPα-knockout (KO) mice using the K/BxN serum-transfer model. The contribution of radiosensitive and radioresistant cells to disease was evaluated by reciprocal bone marrow transplantation. RESULTS: RPTPα was enriched in the RA synovial lining. RPTPα knockdown impaired RA FLS survival, spreading, migration, invasiveness, and responsiveness to platelet-derived growth factor, tumor necrosis factor, and interleukin-1 stimulation. These phenotypes correlated with increased phosphorylation of Src on inhibitory Y(527) and decreased phosphorylation of FAK on stimulatory Y(397) . Treatment of RA FLS with an inhibitor of FAK phenocopied the knockdown of RPTPα. RPTPα-KO mice were protected from arthritis development, which was due to radioresistant cells. CONCLUSION: By regulating the phosphorylation of Src and FAK, RPTPα mediates proinflammatory and proinvasive signaling in RA FLS, correlating with the promotion of disease in an FLS-dependent model of RA.
[Mh] Termos MeSH primário: Artrite Experimental/genética
Artrite Reumatoide/genética
Fibroblastos/metabolismo
Proteína-Tirosina Quinases de Adesão Focal/metabolismo
Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/genética
Quinases da Família src/metabolismo
[Mh] Termos MeSH secundário: Animais
Articulação do Tornozelo
Apoptose/efeitos dos fármacos
Apoptose/genética
Artrite Experimental/metabolismo
Artrite Reumatoide/metabolismo
Western Blotting
Adesão Celular/efeitos dos fármacos
Adesão Celular/genética
Movimento Celular/efeitos dos fármacos
Movimento Celular/genética
Sobrevivência Celular/efeitos dos fármacos
Sobrevivência Celular/genética
Progressão da Doença
Ensaio de Imunoadsorção Enzimática
Fibroblastos/efeitos dos fármacos
Perfilação da Expressão Gênica
Técnicas de Silenciamento de Genes
Interleucina-1/farmacologia
Camundongos
Camundongos Knockout
Fosforilação/efeitos dos fármacos
Fosforilação/genética
Fator de Crescimento Derivado de Plaquetas/farmacologia
Reação em Cadeia da Polimerase
Transdução de Sinais/efeitos dos fármacos
Transdução de Sinais/genética
Membrana Sinovial/citologia
Fator de Necrose Tumoral alfa/farmacologia
Quinases da Família src/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Interleukin-1); 0 (Platelet-Derived Growth Factor); 0 (Tumor Necrosis Factor-alpha); EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases); EC 2.7.10.2 (src-Family Kinases); EC 3.1.3.48 (Ptpra protein, mouse); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 4)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:170201
[Lr] Data última revisão:
170201
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:150929
[St] Status:MEDLINE
[do] DOI:10.1002/art.39442


  9 / 259 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26111662
[Au] Autor:Xiong YS; Liu FF; Liu D; Huang HZ; Wei N; Tan L; Chen JG; Man HY; Gong CX; Lu Y; Wang JZ; Zhu LQ
[Ad] Endereço:Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Neurological Disorder of Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
[Ti] Título:Opposite effects of two estrogen receptors on tau phosphorylation through disparate effects on the miR-218/PTPA pathway.
[So] Source:Aging Cell;14(5):867-77, 2015 Oct.
[Is] ISSN:1474-9726
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The two estrogen receptors (ERs), ERα and ERß, mediate the diverse biological functions of estradiol. Opposite effects of ERα and ERß have been found in estrogen-induced cancer cell proliferation and differentiation as well as in memory-related tasks. However, whether these opposite effects are implicated in the pathogenesis of Alzheimer's disease (AD) remains unclear. Here, we find that ERα and ERß play contrasting roles in regulating tau phosphorylation, which is a pathological hallmark of AD. ERα increases the expression of miR-218 to suppress the protein levels of its specific target, protein tyrosine phosphatase α (PTPα). The downregulation of PTPα results in the abnormal tyrosine hyperphosphorylation of glycogen synthase kinase-3ß (resulting in activation) and protein phosphatase 2A (resulting in inactivation), the major tau kinase and phosphatase. Suppressing the increased expression of miR-218 inhibits the ERα-induced tau hyperphosphorylation as well as the PTPα decline. In contrast, ERß inhibits tau phosphorylation by limiting miR-218 levels and restoring the miR-218 levels antagonized the attenuation of tau phosphorylation by ERß. These data reveal for the first time opposing roles for ERα and ERß in AD pathogenesis and suggest potential therapeutic targets for AD.
[Mh] Termos MeSH primário: Receptor alfa de Estrogênio/metabolismo
Receptor beta de Estrogênio/metabolismo
MicroRNAs/metabolismo
Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/metabolismo
Proteínas tau/metabolismo
[Mh] Termos MeSH secundário: Doença de Alzheimer/enzimologia
Doença de Alzheimer/metabolismo
Animais
Células Cultivadas
Receptor alfa de Estrogênio/genética
Receptor beta de Estrogênio/genética
Células HEK293
Seres Humanos
Masculino
Camundongos
Camundongos Transgênicos
MicroRNAs/genética
Fosforilação
Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/genética
Proteínas tau/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Estrogen Receptor alpha); 0 (Estrogen Receptor beta); 0 (MIRN218 microRNA, human); 0 (MicroRNAs); 0 (tau Proteins); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 4)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150627
[St] Status:MEDLINE
[do] DOI:10.1111/acel.12366


  10 / 259 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25951993
[Au] Autor:Xu J; Kurup P; Foscue E; Lombroso PJ
[Ad] Endereço:Child Study Center, Yale University School of Medicine, New Haven, Connecticut, USA.
[Ti] Título:Striatal-enriched protein tyrosine phosphatase regulates the PTPα/Fyn signaling pathway.
[So] Source:J Neurochem;134(4):629-41, 2015 Aug.
[Is] ISSN:1471-4159
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The tyrosine kinase Fyn has two regulatory tyrosine residues that when phosphorylated either activate (Tyr(420)) or inhibit (Tyr(531)) Fyn activity. Within the central nervous system, two protein tyrosine phosphatases (PTPs) target these regulatory tyrosines in Fyn. PTPα dephosphorylates Tyr(531) and activates Fyn, while STEP (STriatal-Enriched protein tyrosine Phosphatase) dephosphorylates Tyr(420) and inactivates Fyn. Thus, PTPα and STEP have opposing functions in the regulation of Fyn; however, whether there is cross talk between these two PTPs remains unclear. Here, we used molecular techniques in primary neuronal cultures and in vivo to demonstrate that STEP negatively regulates PTPα by directly dephosphorylating PTPα at its regulatory Tyr(789). Dephosphorylation of Tyr(789) prevents the translocation of PTPα to synaptic membranes, blocking its ability to interact with and activate Fyn. Genetic or pharmacologic reduction in STEP61 activity increased the phosphorylation of PTPα at Tyr(789), as well as increased translocation of PTPα to synaptic membranes. Activation of PTPα and Fyn and trafficking of GluN2B to synaptic membranes are necessary for ethanol (EtOH) intake behaviors in rodents. We tested the functional significance of STEP61 in this signaling pathway by EtOH administration to primary cultures as well as in vivo, and demonstrated that the inactivation of STEP61 by EtOH leads to the activation of PTPα, its translocation to synaptic membranes, and the activation of Fyn. These findings indicate a novel mechanism by which STEP61 regulates PTPα and suggest that STEP and PTPα coordinate the regulation of Fyn. STEP61 , PTPα, Fyn, and NMDA receptor (NMDAR) have been implicated in ethanol intake behaviors in the dorsomedial striatum (DMS) in rodents. Here, we report that PTPα is a novel substrate for STEP61. Upon ethanol exposure, STEP61 is phosphorylated and inactivated by protein kinase A (PKA) signaling in the DMS. As a result of STEP61 inhibition, there is an increase in the phosphorylation of PTPα, which translocates to lipid rafts and activates Fyn and subsequent NMDAR signaling. The results demonstrate a synergistic regulation of Fyn-NMDAR signaling by STEP61 and PTPα, which may contribute to the regulation of ethanol-related behaviors. NMDA, N-methyl-D-aspartate; PTPα, receptor-type protein tyrosine phosphatase alpha; STEP, STriatal-Enriched protein tyrosine Phosphatase.
[Mh] Termos MeSH primário: Corpo Estriado/enzimologia
Proteínas Proto-Oncogênicas c-fyn/fisiologia
Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/fisiologia
Transdução de Sinais/fisiologia
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
EC 2.7.10.2 (Fyn protein, mouse); EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn); EC 3.1.3.48 (Ptpra protein, mouse); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 4)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150509
[St] Status:MEDLINE
[do] DOI:10.1111/jnc.13160



página 1 de 26 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde